3-Substituted -5-alkyl-2-cyclohexen-1-ones

ABSTRACT

3-Substituted-5-alkyl-2-cyclohexen-1-ones and methods for their preparation are disclosed. These novel compounds are useful as intermediates in the preparation of 5-alkyl substituted resorcinols such as olivetol.

United States Patent Brossi et al.

S-SUBSTITUTED -5-ALKYL-2-CYCLOHEXEN-l-ONES Inventors: Arnold Brossi,Riehen, Switzerland;

Antonino Focella; Sidney Teitel, both of Clifton, NJ.

Assignee: Hoffmann-La Roche Inc., Nutley,

Filed: Sept. 23, 1974 Appl. No.: 508,598

Related US. Application Data Division of Ser. No, 414.577 Nov. 9. W73.abandoned which is a division of Ser. No. 181,198.

[ 1 Nov. 11, 1975 [56] References Cited UNlTED STATES PATENTS 1622.588ll/l97l Griot 260/590 OTHER PUBLICATIONS Vandervolle et 211., Bull. Soc.Chim. Belges, Vol. 76, pp. 111-122 1967) Primary Emmirwr-James 0.Thomas, Jr.

Assistant Examiner-James H. Reamer Attorney, Agent, or Firm-Samuel L.Welt; Bernard S. Leon; Frank P. Hoffman 57 ABSTRACT3-Substituted-5-alkyl-2-cyclohexcn-l-ones and methods for theirpreparation are disclosed. These novel compounds are useful asintermediates in the preparation of S-alkyl substituted resorcinols suchas olivetol.

1 Claim, No Drawings S-SUBSTITUTED -5-ALKYL-2-CYCLOHEXEN- l-ONES RELATEDAPPLICATIONS This is a division, of application Ser. No. 414,577 filedNov. 9, 1973, now abandoned, which in turn is a divisional applicationof application Ser. No. 181,198 filed Sept. 16, 1971, now US. Pat. No.3,790,636 which in turn is a divisional of application Ser. No. 793,l9lfiled Jan. 22, 1969 and now abandoned.

BACKGROUND OF THE INVENTION In the past, olivetol IS-n-amyl-resorcinolland other 5-alkyl substituted resorcinols have been synthesized fromstarting materials such as 3,5-dihydroxybenzoic acid. These procedureshave proven extremely disadvantageous due to the fact that the startingmaterials are not readily available. Consequently, these processes haveproven extremely costly. Therefore, it has long been desired to providea simple and economic process for producing 5-alkyl substituted resrcinols from inexpensive starting materials.

SUMMARY OF THE INVENTION In accordance with this invention, it has beenfound that S-alkyl resorcinols of the formula.

HO OH wherein R is an alkyl group containing from I to 26 carbon atoms,can be synthesized economically and in high yields through thecondensation product of acetone and an aldehyde of the formula:

RCHO II wherein R is as above. In this manner, resorcinols of theformula I above, such as olivetol, can be economically prepared fromcheap and readily available starting materials.

DETAILED DESCRIPTION The term lower alkyl" as used herein denotes bothstraight and branched chain alkyl groups containing from 1 to 7 carbonatoms such as methyl, ethyl, propyl, isopropyl, etc. The term loweralkanoic acid denotes lower alkanoic acids having from I to 7 carbonatoms such as formic acid, acetic acid, propionic acid, etc. The termlower alkanol denotes alkanols containing from I to 7 carbon atoms suchas methanol, ethanol, propanol, isopropanol, etc. The term phenyl-loweralkyl as used throughout the specification deontes phenyl-lower alkylgroups containing from 7 to l4 carbon atoms such as benzyl, phenethyl,phenpropyl, etc.

The term alkyl group containing from I to 26 carbon atoms" in formula Iabove includes both straight and branched chain alkyl groups containingfrom 1 to 26 carbon atoms such as methyl, ethyl, n-propyl, isopropyl,n-decyl, dodecyl, n-pentadecyl, octadecyl, heneicosyl.l,2,3-trimethylheptyl, l,2-dimethyloctyl, etc. In accordance with anembodiment of this invention, the process of this invention is directedto producing resorcinols of the formula I above wherein R is an alkylgroup containing from 3 to 15 carbon atoms, and preferably from 5 to 15carbon atoms.

In accordance with the first step of this reaction, an aldehyde of theformula II is condensed with acetone to produce a compound of theformula:

wherein R is as above. This condensation reaction is carried out byreacting a compound of the formula II with acetone in the presence of analkali metal hydroxide such as sodium hy droxide, potassium hydroxide,etc. In carrying out this reaction, excess acetone can be utilized asthe reaction medium. However, if desired, an inert organic solvent canbe utilized as the reaction medium. If desired, any conventional inertorganic solvent can be used as the reaction medium. Among theconventional inert organic solvents which can be utilized, toluene,benzene, xylene, dioxane, ethyl ether and tetrahydrofuran are preferred.This reaction can be carried out at room temperature. However, ifdesired, elevated or reduced temperatures, i.e., temperatures between10C. to C. can be utilized.

The next step of the process of this invention is carried out bydehydrating the compound of formula [11 above to form a compound of theformula:

wherein R is as above.

Any conventional method of dehydrating the compound of the formula IIIabove can be utilized in carry ing out this reaction. Among theconventional dehydrating methods which can be utilized are includedtreating the compound of the formula III above with a dehydrating agentsuch as sodium sulfate, cupric sulfate, etc. This dehydration reactioncan be carried out in an anhydrous solvent medium utilizing refluxtemperatures. Another means for dehydrating the compound of theformula'JIl above is by refluxing the com pound of the formula III in anazeotroping agent such as a conventional azeotropic solvent. Among theazeotropic solvents which are utilized to dehydrate the compound of theformula III above, benzene, xylene, toluene, etc., are preferred.

In the next step, the compound of formula IV is converted to a compoundof formula:

3 wherein R is as above, and R is lower alkyl or phenyl-lower alkyl byreacting the compound of formula IV with a malonic acid ester of theformula:

this invention are included alkali metal hydroxides, such as sodium orpotassium hydroxide, alkali metal amides such as sodamide, etc.; alkalimetal alcoholates; alkali metal hydrides such as sodium hydride,potassium hydride, etcx, basic amines such as pyridine, etc. Thepreferred bases are alkali metal alkoxides such as sodium methoxide andpotassium methoxide.

In this reaction between compounds of the formula VI above withcompounds of the formula IV above, any conventional organic solvent canbe utilized. Among the conventional solvents, the lower alkanols such asmethanol, ethanol, etc., are preferred. Where a lower alkanol containingless carbon atoms than R in the compound Vl above is utilized as theorganic solvent, this alkanol forms the ester group in compounds of theformula V.

The reaction of compounds of the formula W above with compounds of theformula VI above to produce the compound of the formula V above can becarried out by reacting one mole of the compound of the formula lV abovewith one mole of the compound of the formula VI above. In this reaction,a molar excess of either the compound of formula VI above or thecompound of the formula IV above can be present. Furthermore, it isgenerally preferable that the base be present in the reaction medium inan amount of at least one mole per mole of the compound of formula IVabove. However, if desired, the base can be present in excess of thisamount. in carrying out this reaction, temperature and pressure are notcritical, and this reaction can be carried out at room temperature andatmospheric pressure. If desired, elevated or reduced temperatures canbe utilized. Generally, this reaction can be conveniently carried out ata temperature of from 0C. to 100C. depending upon the reflux temperatureof the solvent.

In accordance with this invention, the compound of wherein R and R areas above, and X is selected from the group consisting of chlorine,bromine or iodine.

In accordance with one embodiment of this invention, the compound of theformula V above is converted to the compound of the formula I above, viathe compound of the formula Vll above. in the first step of thisreaction sequence, step (a), the compound of the 55 formula V above isconverted to the compound of the formula VI] above. The reaction of step(a) is carried out by treating the compound of the fonnula V above witha halogenating agent wherein the halogen is bromine, chlorine or iodine.Any conventional halogenat- 60 ing agent can be utilized in carrying outthe reaction of step (a). Among the conventional halogenating agentswhich can be utilized are included, N-bromo'succinimide, alkali metalhypohalites, cupric bromide, cupric iodide or cupric chloride, or ahalogen such as bromine, chlorine or iodine. Generally, this reaction iscarried out in an inert solvent. Any conventional inert solvent can beutilized in carrying out this reaction. Among the conventional inertsolvents which can be utilized in carrying out this reaction, water.acetone, ethanol and the organic acids such as acetic acid, propionicacid. etc., are preferred. Among the organic acid solvents, the loweralkanoic acids such as acetic acid are preferred. it is generallypreferable to utilize water or aqueous organic acids which include loweralkanoic acids such as aqueous acetic acid in carrying out thisreaction. When a halogen such as bromine, chlorine, or iodine isutilized, this halogen is generally added to the reaction mixturedissolved in the inert organic solvent.

ln carrying out the reaction of step (a), it is preferable to add about1 mole of the halogenating agent per mole of the compound of formula Vabove. if desired, a molar excess of the halogenating agent can beutilized in the reaction, i.e., from about 1 to 3.5 moles of thehalogenating agent per mole of the compound of formula V above. Ifdesired, this reaction can be carried out at room temperature. However,any temperature from about 0C. to about 30C. can be utilized in carryingout this reaction.

The conversion of compounds of the formula Vll above to compounds of theformula 1 above, is carried out by heating the compound of the formulaVI] above to a temperature of from 40C. to 130C. It is generallypreferred to carry out the reaction in the presence of inorganic acid oracid salt of organic bases. The presence of these acid or acid saltsspeeds up the reaction. Typical inorganic acids which may be employed inthe above process include hydrohalic acids (especially hydrochloric orhydrobromic acid) and sulfuric acid, as well as the mineral acid saltsof organic bases such as pyridine, with pyridine hydrochloride beingpreferred. This reaction can be carried out in an aqueous or organicsolvent medium. Any conventional inert organic solvent can be utilizedas the reaction medium. On the other hand, the reaction of step (b) cantake place without the use of any solvent such as by heating thecompound of formula Vll above to a temperature of from 40 to 120F. Thisreaction of step (b) can take place at atmospheric pressure. However, ifdesired, elevated pressures can be utilized, i.e., from 50 psig to 1,000psig.

In accordance with another embodiment of this invention, the compound ofthe formula V above can be directly converted to the compound of theformula I above by treating the compound of the formula V above with ahalogenating agent in an inert solvent medium, at a temperature of from40C. to 130C. Any of the conventional halogen ating agents such as thosementioned hereinbefore can be utilized in carrying out the reaction ofstep (c). The halogen should be either chlorine, bromine or iodine.Among the preferred halogenating agents are included cupric halides,such as cupric bromide, cupric chloride, cupric iodide, bromine,chlorine and iodine. in carrying out the reaction of step (c), anyconventional inert solvent can be utilized. Generally, the preferredsolvents are water and the organic acids which include lower alkanoicacids such as acetic acid, propionic acid, etc., or high boiling inertorganic solvents such as xylene, etc. The reaction of step (c) ispreferably carried out at the reflux temperature of the reaction medium.However, temperatures of from about 40C. to about 130C. can be utilized,depending upon the reflux temperature of the solvent medium. Whilereaction temperatures of from 40C. to 130C. can be utilized to completethe reaction, the addition of the halogenating agent to the compound offormula V above should take place at lower temperatures, i.e., fromabout 0 to C.

In accordance with another embodiment of this invention, the compoundsof formula V above can be converted to the compound of formula I abovevia the compound of the formula Vlll above. In this reaction sequence,the compound of the formula V above is first converted to the compoundof the formula Vlll above via reaction step (d). The reaction of step(d) is carried out by treating the compound of the formula V above witha dehydrogenating agent. In carrying out this reaction, any conventionaldehydrogenating agent can be utilized. Among the conventionaldehydrogenating agents which can be utilized, dichlorodicyanoquinone,mercuric acetate and palladium on carbon are preferred. Generally, thisreaction is carried out in a conventional inert organic solvent. Anyconventional inert organic solvent can be utilized. Among theconventional inert organic solvents that can be utilized in thisreaction, benzene, toluene, xylene, organic acids which include loweralkanoic acids such as acetic acid are preferred. When palladium oncarbon is utilized as the dehydrogenating agent, no solvent need bepresent and the reaction can be carried out by heating the compound to atemperature of from about 150C. to about 300C. When a solvent isutilized, the reaction proceeds very slowly at room temperature.Therefore, it is generally preferred to utilize elevated temperatures incarrying out this reaction. In general, temperatures from about 50C. toC. are preferred depending upon the reflux temperature of the solventutilized in the reaction medium.

The compound of formula Vlll above can, if desired, be prepared from thecompound of formula Vll above via reaction step (e). This reaction iscarried out by treating the compound of the formula Vll above withorganic amine base. Any conventional organic amine base such as thebases hereinbefore mentioned can be utilized. Among the conventionalbases which can be utilized, pyridine, triethanolamine, etc., arepreferred. in carrying out the reaction of step (e), an inert organicsolvent medium can be utilized. Any conventional inert organic solventcan be utilized in carrying out this reaction. Among the conventionalinert organic solvents, solvents such as benzene, tetralin, decalin,xylene and 1,2,4-trichlorobenzene are preferred. This reaction ispreferably carried out at temperatures of from about 40C. to C.,depending upon the reflux temperature of the reaction medium. However,this reaction can be easily carried out at room temperature, i.e.,temperatures of from 20C. to 35C.

The compound of formula Vlll above is converted to the compound offormula 1 above via reaction step (f). The reaction step (f) is carriedout by first saponifying the compound of the formula Vlll above with anyconventional saponifying agent to fonn the compound of the formula VII]above wherein R is hydrogen and thereafter decarboxylating the compoundof the for mula Vlll above. In saponifying the compound of the formulaV111, any conventional saponifying agent and method of saponificationcan be utilized. Among the conventional saponifying agents which can beutilized are included the inert alkali metal hydroxides such as sodiumhydroxide and potassium hydroxide utilizing conventional inert organicsolvents or an aqueous medium. in carrying out the saponificationreaction, temperature and pressure are not critical, and this reactioncan be carried out at room temperature and atmospheric pressure.However, elevated temperatures up to the reflux temperature of thesolvent can be utilized.

The decarboxylation step is carried out by treating the saponifiedcompound of formula Vlll above with an inorganic acid. Any of theconventional inorganic acids such as the hydrohalic acids can beutilized in carrying out this reaction. This reaction can be carried outin an inert organic solvent or aqueous medium. In carrying out thisreaction, temperature and pressure are not critical. Therefore, thisreaction can be carried out at room temperature and atmosphericpressure. However, if desired, elevated or reduced temperatures andpressures can be utilized.

In accordance with another embodiment of this invention, the compound ofthe formula V above can be converted to the compound of the formula Iabove via the compound of the formula lX above. In the first step ofthis reaction, the compound of the formula V above is converted to thecompound of the formula lX above via reaction step (g). The reactionstep (g), is carried out by treating the compound of the formula V witha halogenating agent in the presence of an organic base preferablypyridine. [n carrying out the reaction of step (g), the halogen of thehalogenating agent utilized should be bromine, chlorine or iodine, andat least 2 moles of the halogenating agent should be present per mole ofthe compound of the formula V above. Any of the halogenating agentsdescribed in connection with step (a) can by utilized in carrying outthe reaction of step (g). If desired, a molar excess of the halogenatingagent can be present, i.e., from about 2 to about 6 moles of thehalogenating agent per mole of the compound of formula V above. Thereaction of step (g) is carried out in the presence of an organic base.The or ganic base can be present in catalytic amounts. lf desired, theorganic base can be added to the reaction medium in large amounts, i.e.,from about 1 mole to about 6 moles of the organic base per mole of thehalogen. ln carrying out this reaction, any conventional inert organicsolvent can be utilized. Among the conventional inert organic solventswhich can be utilized are included, dimethylformamide, benzene, toluene,etc. Generally, this reaction is carried out in an anhydrous medium.Furthermore, in carrying out this reaction, temperatures of from about50C. to about 20C. can be utilized. Generally it is preferred to carryout this reaction at a temperature of from 3 5C. to about 5C.

The compound of formula lX above is converted, via step (h), to thecompound of formula 1 above by hydrogenating the compound of formula IXwith a palladium catalyst in the presence of an alkali metal hydroxideat elevated pressures. Any conventional palladium catalyst such aspalladium, palladium on carbon, etc., can be utilized in carrying outthis hydrogenation reaction. In carrying out this reaction, anyconventional alkali metal hydroxide such as sodium hydroxide orpotassium hydroxide can be utilized. The palladium catalyst and thealkali metal hydroxide can be present in the reaction medium incatalytic quantities. However, if desired, large excess of the palladiumcatalyst or the alkali metal hydroxide can be utilized. Generally, thisreaction is carried out in a conventional inert organic solvent. Anyconventional inert organic solvent such as the solvents hereinbeforementioned can be utilized. The reaction of step (h) is carried out undera hydrogen pressure of from about 50 psig to about 1,000 psig. In thisreaction temperature is not critical and room temperature can beutilized. However, if desired, elevated temperatures can be utilized incarrying out this reaction. Generally, this reaction can be carried outat a temperature of from about C. to about 150C.

In accordance with another embodiment of this invention, the compound ofthe formula V above is converted to the compound of the formula I viacompounds of the formulae X, XI and Xll. [n this embodiment, thecompound of the formula V above is first converted into the compound ofthe formula X above via reaction step (i) by saponification anddecarboxylation. The saponification step converts R into hydrogen in thecompound of the formula V above and this sa ponified product is thendecarboxylated to form the compound of formula X above. The reaction ofstep (i) is carried out utilizing the same conditions described inconnection with reaction step (f).

The compound of formula X above can be converted into the compound ofthe formula XI above via reaction step (j) by treating the compound ofthe formula X above with a halogenating agent in the manner described inconnection with step (a).

The preferred method of halogenation is to treat the compound of formulaX with an alkali metal hypohalite in an aqueous medium in the presenceof an alkali metal hydroxide.

In accordance with another embodiment of this invention, the compound ofthe formula Xl above can be prepared from a compound of the formula Vllabove via reaction step (k). Reaction step (k) is carried out by firstsaponifying the compound of the formula VI] so that R in the compound ofthe formula Vll is hydrogen. This saponified product is thendecarboxylated to form a compound of the formula Xl above. Thesaponification and decarboxylation in reaction step (k) is carried oututilizing the same conditions and in the same manner described inconnection with reaction step (f). The decarboxylation in step (k) isgenerally carried out at temperatures of from 0 to 30C.

The compound of formula Xl is converted to the compound of formula Xllby treating the compound of formula Xl with a dehydrogenating agent asdescribed in connection with reaction step (d). The same conditionsutilized in connection with reaction step (d) are utilized in connectionwith reaction step (1). The preferred dehydrogenating agent for use incarrying out reaction step (1) is mercuric acetate in an organic acidsolvent such as acetic acid.

The compound of the formula Xll above is converted into the compound ofthe formula I above via reaction step (m) by hydrogenating the compoundof the formula Xll above with a palladium catalyst under elevatedpressure. The same conditions described in connection with reaction step(h) are utilized in carrying out the reaction of step (m).

In connection with another embodiment of this invention, the compound ofthe formula X above can be converted into the compound of the formula Iabove by means of the following reaction scheme:

wherein R and R, is lower alkyl or phenyl-lower alkyl and R is as above.

In accordance with this embodiment, the compound of formula X isconverted to the compound of the formula I above via compounds of theformulae XIII and XIV. The compound of formula X above can be convertedto the compound of formula XIII above by any conventional means of etherification. Among the meth ods of etherification which can be utilizedto form the compound of formula XIII is to treat the compound of formulaX with a lower alkanol such as methanol, ethanol, etc, or phenylloweralkanol in the presence of a mineral acid such as hydrogen bromide,hydrogen chloride, etc. This reaction can be carried out, if desired, inan inert organic solvent medium. On the other hand, the lower alkanol orthe phenyl-lower alkanol itself can be utilized as the solvent medium.In this reaction, tern perature and pressure are not critical, and thisreaction can be carried out at room temperature and atmospheric pressureor at elevated temperatures and pressures.

In accordance with this invention, either the compound of formula XIIIabove or the compound of formula X above can be converted to thecompound of formula XIV above by treating either the compound of formulaX or the compound of formula XIII above with cupric halide such ascupric chloride, cupric bromide, etc.. in the presence ofa lower alkanolor phenyl-lower alkanol. This reaction can be carried out, if desired,in a conventional inert organic solvent. On the other hand, the loweralkanol can be utilized as the solvent medium. In carrying out thereaction of either step or step (r), temperature and pressure are notcritical, and these reactions can take place at room temperature andatmospheric pressure. On the other hand, elevated temperatures andpressures can be utilized if desired.

In accordance with a preferred embodiment of this invention the processof step (0) above can produce a new compound of the formula:

R 0 OIL,

wherein R is as above, R and R are independently selected fromphenyl-lower alkyl or lower alkyl with the proviso that the ether formedby R is a different ether from the ether formed by R compound of formulaXIV-A can be formed from 10 3-isopropoxy-5-methoxy-n-pentylbenzene.

The compound of the formula XIV above is converted into the compound ofthe formula I above by any conventional method of ether hydrolysis.Among the conventional methods of ether hydrolysis that can be utilizedin carrying out reaction step (p), it is generally preferred to treatthe compound of the formula XIV with a mineral acid and salts of organicamine bases, such as those mentioned hereinbefore. Among the preferredare included, hydrobromic acid, and pyridine hydrochloride. Generally,this reaction is carried out in the presence of an inert organicsolvent. Any conventional inert organic solvent such as the solventsmentioned hereinbefore can be utilized. In carrying out this reaction,temperature and pressure are not critical, and this reaction can becarried out at room temperature and atmospheric pressure. However, ifdesired, elevated temperatures and pressures can be utilized.

In accordance with another embodiment of this in-- vention, the compoundof the formula X above can be directly converted to the compound of theformula I above as in reaction step (q). This reaction is carried out bytreating the compound of the formula X above with a dehydrogenatingagent. The same conditions described in connection with reaction step(d) can be utilized in carrying out the reaction of step (q). Among thepreferred dehydrogenating agents which can be utilized in carrying outreaction step (q), mercuric acetate is preferred. The preferred solventin this reaction is an organic acid solvent such as acetic acid.

The process of this invention can be utilized in preparing a variety ofresorcinols. By means of the process of this invention, the followingaldehydes can be converted to the following resorcinols via thefollowing 2- hydroxy-4oxo-cyelohexe2-ene-l-carboxylates of formula Vabove:

hexanal to 5-(n-pentyl)-resorcinol viamethyl-6mpentyl-2-hydroxy-4-oxo-cyclohex-2-enel -carboxylate;

butanal to 5-( n-propyl)-resorcinol viamethyl-6-npropyl-2-hydroxy-4-oxo-cyclohex-2-enel-carboxylate;

octanal to S-mheptyl-resorcinol viamethyl-6-n-heptyl-2-hydroxy-4-oxo-cyclohex-2-enel -carboxylate;

Z-methyl-octanal to 5-( l-methylheptyl)-resorcinol via methyl2-hydroxy-4-oxo-6-( l-methylheptyl )-2- cyclohexenel -carboxylate;

hendecanal to 5-(n-decyl)-resorcinol via methyl-2- hydroxy-4-oxo-6-(n-decyl )-2-cyclohexenel -carboxylate;

hexadecanal to S-(n-pentadecyl)resorcinol via methyl-2-hydroxy-4-oxo-6-(l-pen tadecyl )-2- cyclohexene l -carboxylate;

docosanal to S-heneicosyl resorcinol via methyl-2-hydroxy-4-oxo-6-(heneicosyl )-2-cyclohexenel carboxylate; and

hexacosanal to 5-pentacosyl resorcinol via methyl-2- hydroxy-4-oxo-6-(pentacosyl )-2-cyclohexenel carboxylate.

The resorcinols produced in accordance with the process of thisinvention have a variety of uses. S-npentyl resorcinol (olivetol) is animportant intemiediate in the preparation of tetrahydrocannabinols (theactive constituent of marijuana). Furthermore, alkyl resorcinols such asn-propyl resorcinol, n-butyl resorcinol, n-hexyl resorcinol, n-heptylresorcinol, n-decyl resorcinol, etc., are well known bactericides.Furthermore, higher alkyl resorcinols such as -n-heneicosylresorcinoland S-nonadecyl resorcinal are food additives which are found naturallyin wheat bran. Therefore, the process of this invention provides asimple and economic means for synthesizing valuable resorcinols.

The invention will be more fully understood from the specific exampleswhich follow. These examples are intended to illustrate the invention,and are not to be construed as limitative thereof. The temperatures ofthese examples are in degrees Centigrade, and the ether utilized inthese examples is diethyl ether.

EXAMPLE l Into a 2-liter three neck flask fitted with a reflux condensertopped with a N gas inlet tube attached to a constant pressure mercurygauge. mechanical stirrer, dropping funnel and thermometer were placed230 ml. of anhydrous methanol (reagent grade) and 32.4 g. (0.60 mole) ofsodium methoxide. A slow current of N gas was introduced and the mixturewas stirred until a complete solution was obtained. One hundred and tengrams (0.68 mole) of diethyl malonate was added, the solution wasstirred for an additional minutes and 75 g. (0.48 mole) of 90% pure3-nonene-2-one was added portionwise at a rate such that the reactiontemperature was kept below the boiling point (ca. 5060). Stirring andrefluxing were continued for 3 hours. The reaction mixture was allowedto cool to room temperature, neutralized with concentrated HCl 50 ml.)and allowed to stand overnight. The solvent was distilled under reducedpressure and the residue was partitioned between 200 ml. of l N HCl and800 ml. of ethyl acetate. The aqueous layer was separated and theorganic phase was washed with two 300 ml. portions of water and theproduct was then extracted from the ethyl acetate with a saturatedsolution of sodium bicarbonate until a small portion on acidification nolonger gave a turbid solution five 200 ml. portions). The sodiumbicarbonate solution was cautiously acidified and extracted with three300 ml. portions of ether. The ether solution was dried over sodiumsulfate and distilled under reduced pressure. The semi-solid residue wasdried at 50 under high vacuum for 5 hours to yield methyl6-n-pentyl-2-hydroxy-4-oxo-cyclohex-2-enecarboxylate as a white solid,m. p. 8385.

EXAMPLE 2 Into a 2-liter three neck flask fitted with a refluxcondenser, mechanical stirrer, dropping funnel and thermometer wereplaced 60 g. (0.25 mole) of methyl 6-npentyI-Z-hyd roxy-4-oxo-cyclohex-2-enel-carboxylate, 200 ml. of acetic acid and 200 ml. of water.The mixture was stirred vigorously until a fine suspension was obtained,cooled and maintained at 5-l0 while 44.4 g. (0.28 mole) of bromine.dissolved in 70 ml. of acetic acid, was added dropwise over a period of2 hours. The reaction was stirred at room temperature for 1 hour andthen diluted with 500 ml. of water and allowed to stand at 510overnight. The solids were filtered, washed with cold water (ca. three75 ml. portions) until the washings gave a negative test for bromine anddried in a vacuum oven at 50 for 4 hours to give methyl 3-bromo-2-hydroxy-4-oxo-6-n-pentyl-cyclohex-2-enel carboxylate, m. p.100102.

EXAMPLE 3 placed 60 g. (0.182 mole) of methyl 3-bromo-2-hydroxy-4-oxo-6-n-pentylcyclohex-Z-ene-1-carboxylate and 90 g. (0.75mole) of anhydrous pyridine hydrochloride. The semi-solid mixture washeated in an oil bath at 90 for 4 hours (internal temperature 8284) andthen at 200 for 2 hours. The reaction mixture was cooled to roomtemperature and partitioned between 550 ml. of ether and 100 ml. of 1.2N HCl. The aqueous layer was separated and the ether phase washed with50 ml. of 1.2 N HCI and then with ml. of water. The organic phase wasthen washed with two 75 ml. portions of 10% sodium hydrosulfite(dithionite) followed by two 75 ml. portions of saturated NaHCO and thenwith 75 ml. of water, dried over anhydrous Na SO and the solventevaporated under reduced pressure. The dark oil (34.6 g.) was distilledat 125130/0.05 mm Hg. to yield Olivetol.

EXAMPLE 4 30 g. (0.25 mole) of 92.4% pure 3-hepten-2-one and 52 g. (0.32mole) of diethyl malonate were reacted in the manner of Example 1 toproduce methyl 2- hydroxy-4-oxo-6-n-prop yl-2-cyclohexenel -carboxylateas a white solid, m. p. 9598.

EXAMPLE 5 3 g. (0.014 mole) of methyl2-hydroxy-4-oxo-6-npropyl-Z-cyclohexene-l -carboxylate was reacted inthe manner of Example 2 with 2.3 g. (0.014 mole) of bromine to produce,after crystallization from ethyl acetate, methyl3-bromo-2-hydroxy-4-oxo-6-n-propy1-2- cyclohexenel-carboxylate.

EXAMPLE 6 6 g. (0.021 mole) of methyl 3-bromo-2-hydroxy-4-oxo-6-n-propyl-2-cyclohexene-l-carboxylate was reacted in the manner ofExample 3 with 9 g. (0.105 mole) of anhydrous pyridine HCl to giveS-n-propylresoroinol as a brown oil which was crystallized from waterand melted at 48-50.

EXAMPLE 7 192 g. (0.97 mole) of pure 3-undecene-2-one was reacted in themanner of Example 1 with 262 g. (1.65 moles) of diethyl malonate to givemethyl-2- hydroxy-4-oxo-6-n-hep tyl-2-cyclohexene- 1 -carboxylate as awhite solid, m. p. 7578.

EXAMPLE 8 268 g. (1 mole) of methyl2-hydroxy-4-oxo-6-n-heptyl-2-cyclohexene-l-carboxylate was reacted inthe manner of Example 2 with 176 g. (1.1 moles) of bromine to givemethyl 3-bromo-2-hydroxy-4-oxo-6-nheptyl-Z-cyclohexene-l-carboxylate asa white solid melting at 84-87.

EXAMPLE 9 Into a 3-liter three neck flask fitted with a reflux condenserwith a Dean-Stark attachment, mechanical stirrer and thermometer wereplaced 348 g. (1 mole) of methyl 3-bromo-2-hydroxy-4-oxo'6-n-heptyl-2-cyclohexene-l-carboxylate and 522 g. (4.6 moles) of anhydrous pyridinehydrochloride. The semi-solid mixture was heated in an oil bath at for 4hours (internal temperature 8284). The oil bath was replaced with amantle and the reaction mixture was heated (volatiles removed by meansof the Dean-Stark takeoff) until the internal temperature reachedl90-200 and maintained in this range for 2 hours. The reaction mixturewas cooled to room temperature and partitioned between 3 liters of etherand 660 ml. of 1.2 N HCl. The aqueous layer was separated and the etherphase washed with 300 ml. of 1.2 N HCl and then with two 300 ml.portions of water. The ether solution was extracted with four 350 ml.portions of a NaOH solution and the combined sodium hydroxide extractswere extracted with two 300 ml. portions of ether. The alkaline aqueoussolution was acidified with concentrated hydrochloric acid 700 ml.) andre-extracted with three 800 ml. portions of ether. The combined etherextracts were washed with three 300 ml. portions of 10% sodiumhydrosulfite followed by two 300 ml. portions of saturated NaHCO andthen with 300 ml. of water. dried over anhydrous Na SO and the solventevaporated under reduced pressure. The dark oil (172.5 g.) wasdistilled. The forerun boiling at 140-l50/0.03 mm Hg. (8 g.) wasdiscarded and the fraction boiling at l50l55/0.02 mm Hg. was collectedto give S-n-heptylresorcinol.

EXAMPLE 10 g. (0.078 mole) of 96.6% pure 5-methylundec-3- en-Z-one wasreacted in the manner of Example 1 with 19 g. (0.12 mole) of diethylmalonate to give methyl-2- hydroxy-4-oxo-6-( 1 -methylheptyl)-2-cyclohexene- 1 carboxylate as a white solid, m. p. 8086.

EXAMPLE 1 1 20.2 g. (0.07 mole) of methyl-2-hydroxy-4-oxo-6-(lmethylheptyl)-2-cyclohexene-l-carboxylate was reacted in the manner ofExample 2 with 12 g. (0.072 mole) of bromine to produce 25.7 g. of crudemethyl 3-bromo-2-hydroxy-4-oxo-6( l-methylheptyl)-2-cyclohexene-l-carboxylate. The crude methyl 3- bromo-2-hydroxy-4-oxo-6(l-methylheptyl )-2- cyclohexene-l-carboxylate was treated with 32 g.(0.27 mole) of anhydrous pyridine hydrochloride by the procedure setforth in Example 3 to give 5-( l-methylheptyl)resorcinol as a colorlessoil boiling at l29/0.04 mm Hg.

EXAMPLE 12 A mixture of 5 g. (0.021 mole) of methyl 6-n-pentyl-2-hydroxy-4-oxo-cyclohex-2-ene-l-carboxylate, 5.5 g. (0.021 mole) ofiodine and 50 ml. of acetic acid was stirred at room temperature for 24hours. The solvent was evaporated under reduced pressure and the residuepartitioned between water and ethyl acetate. The aqueous phase wasseparated and the ethyl acetate solution extracted with two 100 ml.portions of sodium bicarbonate. The bicarbonate solution was acidifiedand extracted with two 100 ml. portions of ethyl acetate. The ethylacetate extracts were combined, washed with water, dried over anhydroussodium sulfate and evaporated under reduced pressure to give methyl3-iodo-2- hydroxy-4-oxo-6-n-pentyl-2-cyclohexene- 1 -carboxylate, .m. p.1091 12.

EXAMPLE 13 A mixture of 2.4 g. (0.01 mole) of methyl 6-n-pentyl-2-hydroxy-4-oxo-cyclohex-2-ene- [-carboxylate and 3.4 g. (0.015 mole) ofdichlorodicyanoquinone in 100 ml. of benzene was stirred and refluxedfor 8 hours. The reaction mixture was allowed to cool to roomtemperature and the precipitate filtered. The filtrate was washed withwater. then with two 75 ml. portions of a 10% Na CO solution and thenextracted with two ml. portions of a 5% NaOH solution. The sodiumhydroxide solution was acidified with 6 N hydrochloric acid andextracted with two 150 m1. portions of ethyl acetate. The organic phasewas washed with water, dried over anhydrous sodium sulfate and distilledunder reduced pressure to give methyl 2,4-dihydroxy-6-npentylbenzoate asa viscous oil.

EXAMPLE 14 A mixture of 2.4 g. (0.01 mole) of methyl 6-n-pentyl-2-hydroxy-4-oxo-cyclohex-2-ene-1-carboxylate and 1.5 g. of 25% Pd/C washeated at 230-240 for 3 hours. The reaction mixture was allowed to coolto room temperature, 100 ml. of benzene was added and the resultingsuspension warmed on a steam bath and filtered hot. The filtrate wasdried over anhydrous sodium sulfate and evaporated under reducedpressure to give 0.9 g. (38%) of methyl 2,4-dihydroxy-6-n-pentylbenzoateas a viscous oil.

EXAMPLE 15 A mixture of 2.4 g. (0.01 mole) of methyl 6-n-pentyl-2-hydroxy-4-oxo-eyclohex-2-enel -carboxylate and 3.4 g. (0.011 mole) ofmercuric acetate in 50 ml. of acetic acid was stirred and refluxed for 4hours, cooled to room temperature and the solution decanted from themetallic mercury. The solvent was distilled under reduced pressure andthe residue partitioned between 100 ml. of ethyl acetate and 50 ml. ofwater. The organic phase was extracted with two 100 ml. portions ofsodium bicarbonate, two 50 ml. portions of 1% NaOH solution and thenwith 50 ml. of water, dried over anhydrous sodium sulfate and evaporatedunder reduced pressure. The oily residue 1.3 g.) was crystallized fromether to give methyl 2,4-dihydroxy-6-n-pentylbenzoate, m. p. 7375.

EXAMPLE 1 6 A mixture of 6.4 g. (0.02 mole) of methyl 3- iodo-2-hydroxy-4-oxo-6-n-pen tyl-cyclohex-2-enelcarboxylate and 2 g. (0.022mole) of pyridine in 50 ml. of 1,2,4-trichlorobenzene was stirred at l00(internal temperature) for 2 hours. The mixture was cooled, washed withtwo 25 ml. portions of 1.2 N HCl, then with two 30 ml. portions ofwater, followed by two 40 ml. portions of a 1:1 parts by volume mixtureof saturated solution of sodium bicarbonate and sodium carbonate andthen extracted with three ml. portions of 5% by weight NaOH solution.The alkaline solution was acidified with 6 N HCl and extracted withthree 100 ml. portions of ethyl acetate. The combined ethyl acetateextracts were washed with water. dried over anhydrous Na SO andthe'solvent removed under reduced pressure to give methyl2,4-dihydroxy-6-n-pentylbenzoate as a viscous oil.

EXAMPLE 17 A mixture of 4.8 g. (0.02 mole) of methyl 6-n-pentyl-Z-hydrox y-4-oxo-cyclohex-2-ene- 1 -carboxylate and 100 ml. of aceticacid was stirred vigorously at 75 until a fine suspension was obtained.The mixture was cooled and maintained at 5l0 while a solution of 3.9 g.(0.021 mole) of bromine dissolved in 10 ml. of acetic acid was addeddropwise over a period of 1 hour. The reaction mixture was allowed tostir at room temperature for 1 hour and then on a steam bath for 3hours. The solvent was evaporated under reduced pressure 15 and the oilyresidue dissolved in 200 ml. of ether, washed with two 25 m1. portionsof 10% sodium hydrosulfite, followed by two 25 ml. portions of saturatedNal-lCO and then with water, dried over anhydrous Na SO and evaporatedunder reduced pressure to give Olivetol.

EXAMPLE [8 A mixture of 4.8 g. (0.02 mole) of methyl 6-n-pentyl-2-hydroxy-4-oxo-cyclohex-2-enel -carboxylate and 5.6 g. (0.021 mole) ofiodine in 200 ml. of acetic acid was stirred and heated to reflux for 10hours. The solvent was removed under reduced pressure and the oilyresidue was dissolved in 250 ml. of ether and washed with two 50 ml.portions of water. The ether layer was then washed with two 25 ml.portions of an aqueous solution containing 10% by weight sodiumhydrosulfite, followed by two 25 ml. portions of saturated NaHCQ; andthen with water, dried over anhydrous 1 la SO and the solvent evaporatedunder reduced pressure to give Olivetol.

EXAMPLE 19 A mixture of 12.2 g. (0.05 mole) of methyl6-n-pentyl-2-hydroxy-4-oxo-cyclohex2-ene- 1 -carboxy1ate and 100 ml. ofacetic acid was stirred vigorously at 25 until a fine suspension wasobtained. It was cooled and maintained at 10 while 22.4 g. (0.1 mole) ofeuprie bromide dissolved in 25 ml. of acetic acid was added dropwiseover a period of 1 hour. The reaction mixture was allowed to stir atroom temperature for 1 hour and then at steam bath temperature for 3hours. The solvent was evaporated under reduced pressure and the residuepartitioned between 200 ml. of water and 300 ml. of ether. The etherextracts were washed with two 50 ml. portions of an aqueous solutioncontaining by weight sodium hydrosulfite, followed by two 35 ml.portions of saturated NaHCO and then with 75 ml. of water, dried overanhydrous Na SO and the solvent evaporated under reduced pressure togive Olivetol.

EXAMPLE A mixture of 52 g. (0.16 mole) of methyl 3bromo-2-hydroxy-4-oxo-6-n-pentyl-cyc1ohex-2-ene-1-carboxylate and 200 ml. ofconcentrated hydrochloric acid in 100 m1. of acetic acid was stirred andrefluxed for 14 hours. The solvent was removed under reduced pressureand the residue was dissolved in 500 ml. of ether. The organic phase waswashed with 200 ml. of water, then with two 50 ml. portions of anaqueous solution containing 10% by weight of sodium hydrosulfite,followed by two 75 ml. portions of saturated NaHCO and then with 75 ml.of water and dried over anhydrous Na SO,. The solvent was evaporatedunder reduced pressure to give a dark oil (28.8 g.) which was distilledat l135/0.2 mm Hg. to yield Olivetol.

EXAMPLE 21 A mixture of 52 g. (0.16 mole) of methyl 3-bromo-2-hydroxy-4-oxo-6m-penty1-cyclohex-2-ene- 1 -carboxylate and 200 ml. of anaqueous solution containing 48% by weight of hydrobromic acid in 100 ml.of acetic acid was stirred and refluxed for 3 hours. The solvent wasremoved under reduced pressure and the residue was dissolved in 500 ml.of ether. The ether phase was washed with two 100 ml. portions of waterand then with two 50 m1. portions of 10% sodium hydrosulfite, followedby two 75 ml. portions of saturated Nal-lCO 16 and then with ml. ofwater, dried over anhydrous M1 80, and the solvent evaporated underreduced pressure. The dark oil (301 g.) distilled at l30140/0.2 mm Hg.to yield Olivetol.

EXAMPLE 22 A mixture of 24 g. (0.1 mole) of methyl2,4-dihydroxy-6-n-pentylbenzoate and 200 ml. of a 10% by weight NaOHsolution was heated on a steam bath for 7 hours. The solution wascooled, extracted with two ml. portions of ether, and slowly acidifiedwith concentrated hydrochloric acid. The aqueous phase was heated atsteam temperature for 1 hour longer, cooled and extracted with three 200ml. portions of ether. The extracts were combined, washed with two 75ml. portions of water, then with two 50 ml. portions of an aqueoussolution containing 10% by weight of sodium hydrosulfite. followed bytwo 50 ml. portions of water, dried over anhydrous M1 80, and thesolvent was removed under reduced pressure to give Olivetol.

EXAMPLE 23 A solution of 50 g. (0.208 mole) of methyl6-n-pentyl-2hydroxy-4-oxo-eyelohex-2-ene- 1 -carboxylate in 200 ml. ofan aqueous solution containing 20% by weight of NaOH was heated on asteam bath for 2.5 hours, cooled and extracted with two 100 ml. portionsof ether. The alkaline aqueous solution was acidified slowly with about80 ml, of concentrated hydrochloric acid. The resulting aqueous mixturewas stirred and heated on a steam bath for 1 hour longer, cooled andextracted with three 200 ml. portions of ether. The ether extracts werewashed with water, dried over anhydrous sodium sulfate and the solventwas evaporated under reduced pressure. The residue was treated twicewith 50 m1. of benzene, distilling the solvent each time, to leave3-hydroxy-5-n-penty1-2-eyc1ohexene-l-one as a viscous oil whichsolidified on standing.

EXAMPLE 24 A solution of 30 g. (0.094 mole) of methyl 3-bromo-2hydroxy-4-oxo-6-n-pentyl-eyc1ohex-2-ene- 1 -carboxylate in 200 m1. ofan aqueous solution containing 10 70 by weight of NaOH was heated on asteam bath for 2 hours. The mixture was cooled to 05 which wasmaintained while 6 N HCl was added slowly with stirring until an acidicsolution was obtained. The reaction mixture was allowed to warm to roomtemperature and stirred overnight. The resulting semi-solid mixture wasdissolved in 500 m1. of ethyl acetate, washed with three 50 ml. portionsof water and extracted with three 150 ml. portions of saturated aqueousNaHCO The stirred bicarbonate solution was acidified with dilute HCl andthe mixture allowed to stand overnight. The precipitate was filtered,washed with water and dried in a vacuum oven at 50 for 4 hours to give2-bromo-3-hydroxy-5mpenty1-2-cyclohexene-l-one, m. p. 138.

EXAMPLE 25 with 6 N HCl and allowed to stir overnight. The precipitatethat formed was filtered, washed with water and 17 dried to give2-chloro-3-hydroxy-5-n-pentyl 2- cyclohcxcn-l-one, m. p. l25l29.

EXAMPLE 26 A mixture of 4.3 g. (0.02 mole) of 2-chloro-3-hydroxy-S-n-pentyl-2-cyclohexen-l-one, 6.4 g. (0.02 mole) of mercuricacetate in 120 ml. of acetic acid'was stirred and refluxed for 4 hours.The solution was decanted from the metallic mercury and the solvent wasremoved under reduced pressure. The oily residue was dissolved in 200ml. of an aqueous solution containing by weight NaOH, 10 g. of sodiumhydrosulfite was added and the mixture was heated at 50 for minutes withoccasional shaking. The mixture was allowed to cool to room temperatureand filtered by gravity. The filtrate was extracted with two 50 ml.portions of ether and acidified with 6 N HCl and extracted with three 75ml. portions of ether. The combined ether extracts were washed withthree 50 ml. portions of sodium bicarbonate. dried over anhydrous Na SOand the solvent was removed under reduced pressure. The oily residue waspurified by dry column chromatography, using silica gel as the absorbentand a mixture of 97 parts by volume benzene: 3 parts by volume ethylacetate as the developing agent, to give 2-chloro-5-n-pentylresorcinol:b. p. 300/760 mm Hg.

EXAMPLE 27 A stirred mixture of 24 g. (0.1 mole) of methyl6-npentyl-2-hydroxy-4-oxo-cyclohex-2-enel-carboxylate, 50 ml. ofpyridine and 50 ml. of dimethylformamide was stirred and cooled at -30and maintained at this temperature while 48 g. (0.3 mole) of bromine wasadded dropwise over a period of 2 hours. The reaction mixture wasallowed to warm to room temperature, stirred at this temperatureovernight and the volatiles were evaporated under reduced pressure. Theresidue was dissolved in 800 ml. of ethyl acetate, washed with three 100ml. portions of water and then with three 250 ml. portions of asaturated NaHCO The organic phase was extracted with three 150 ml.portions of an aqueous solution containing 5% by weight of NaOH, thealkaline aqueous solution acidified with 6 N HCl and extracted with two400 ml. portions of ethyl acetate. The organic extract was dried overl\la SO and the solvent was removed under reduced pressure to give 3,5-dibromo-2,4-dihydroxy-6-n-pentylbenzoic acid methyl ester as a dark oil.

EXAMPLE 28 A solution of 91 g. (0.5 mole) of3-hydroxy-5-n-pentyl-2-cyclohexene-1-one in 300 ml. of 5% by weight ofhydrogen bromide in methanol was stirred at room temperature for 24hours. The volatiles were removed under reduced pressure and the oilyresidue was dissolved in 700 ml. of ether, extracted with four 150 ml.portions of a saturated aqueous Na CO solution, washed with 150 ml. ofwater, dried over anhydrous M1 50, and then distilled at l09/0.06 mm Hg.to give 3-methoxy-5 -n-pentyl-2-cyclohexenel -one.

EXAMPLE 29 A mixture of 18 g. (0.1 mole) of3-hydroxy-5-n-pentyl-2-cyclohexene-l-one and 34.1 g. (0.2 mole) ofcupric bromide in 300 ml. of methanol was stirred at room temperaturefor 24 hours, filtered and the filtrate evaporated under reducedpressure. The residual oil was partitioned between 300 ml. of ether and150 ml.

18 of water. The ether layer was separated, washed with two 150 ml.portions of saturated Na CO solution, 100 ml. of water and dried overanhydrous Na SO, and evaporated. The dark oil was fractionally distilledto give 3,4-dimethoxy-n-amylbenzene, b. p. ll0/0.05 mm Hg.

EXAMPLE 30 A mixture of 3.6 g. (0.02 mole) of3-methoxy-5-npentyl-2-cyclohexene-1-one and 6.8 g. (0.04 mole) of cupricbromide in 100 ml. of methanol was reacted by the procedure given inExample 29 to afford 3,5-dimethoxy-n-amylbenzene.

EXAMPLE 3 1 To a solution of 36 g. (0.2 mole) of3-hydroxy-5-npentyl-Z-cyclohexene-l-one in 500 ml. of acetic acid, 77 g.(0.241 mole) of mercuric acetate was added and the mixture was stirredand refluxed for 7 hours. After standing overnight, the solution wasdecanted from the metallic mercury that had formed and the solvent wasevaporated under reduced pressure. The dark brown oily residue wasdissolved in 400 ml. of an aqueous solution containing 10% by weight ofNaOH, 20 g. of sodium hydrosulfite was added and the mixture was heatedon a steam bath for 30 minutes. Charcoal (3 g.) was then added, themixture was heated for an additional 10 minutes, filtered by gravity andthe cake was washed with an aqueous solution containing 10% by weightNaOH solution. The combined filtrates were neutralized to pH 6.5-7 withconcentrated hydrochloric acid and extracted with three 250 ml. portionsof ether. The ether extracts were washed with two ml. portions of asaturated solution of sodium sulfite, two ml. portions of a 1 part byvolume to a 1 part by volume mixture of saturated solutions of Na CO andNaHCO water, dried over anhydrous M21 and then the solvent wasevaporated under reduced pres sure. The dark oil (31 g.) was distilledusing a small fractionating column. The first fraction (2.4 g.) boilingat 105-l 20/0.1 mm Hg. was discarded and the fraction boiling at l20-l30/0.04 mm Hg. was collected to afford Olivetol.

EXAMPLE 32 A mixture of 2.14 g. (0.01 mole) of2-ch1oro-5-npentylresorcinol and 5.6 g. (0.04 mole) of KOH in 50 ml. ofmethanol was heated in an autoclave with 2 g. of Pd/C at 50 and psig for5 hours. The catalyst was filtered, washed with three 20 ml. portions ofethanol and the filtrate was evaporated under reduced pressure to giveOlivetol.

EXAMPLE 33 A mixture of 3.9 (0.01 mole) of 3,5-dibromo-2,4-dihydroxy-6-n-pentylbe nzoic acid methyl ester and 5.6 g. (0.04 mole) ofKOH in 50 m1. of ethanol was hydrogenated in an autoclave with 2 g. ofPd/C at 50 and 100 psig for 5 hours. The catalyst was filtered, washedwith three 20 ml. portions of ethanol and the combined filtrate wasevaporated under reduced pressure to give Olivetol.

EXAMPLE 34 Into a 2-liter three neck creased flask equipped withthermometer, stirrer, condenser and Hershberg dropping funnel was placed100 ml. of 2.5 N sodium hydroxide and 348 g. (6 moles) of acetone. Themixture (under a nitrogen atmosphere) was heated to 54 with an oil bathand, while stirring rapidly, a solution of 200 g. 2-methyl-l-octanal in232 g. (4 moles) of acetone was added dropwise over a period of 3 hours.After completion of the addition, stirring was continued for anadditional 30 minutes at 54, the reaction mixture was cooled to and 83ml. of 3 N hydrochloric acid was added to pH 4.5. Anhydrous magnesiumsulfate (240 g.) was added with cooling, stirred 30 minutes and themixture filtered. The filtrate was concentrated at reduced pressure togive a residual brown oil weighing 369.2 g.. which was dissolved in lliter of benzene and further dried over anhydrous magnesium sulfate.After removal of the drying agent by filtration, 136.8 g. (0.856 mole)of anhydrous powdered cupric sulfate was added and the mixture wasstirred and refluxed for 18 hours. During this reflux period about 20ml. of water was azeotropically removed with a Dean-Stark assembly. Oncooling to room temperature, the copper sulfate was removed byfiltration and the presscake was washed with three 200 ml. portions ofbenzene. The combined benzene filtrates were concentrated at reducedpressure to give 322.5 g. of a residual brown oil which was distilledthrough a 9-inch Vigreux column. After separation, the product5-methylundec-3-en- 2-one was collected in two fractions: 125.7 g., b.p. 77-80/6.5 mm Hg. and 25.2 g., b. p. 80-83.

EXAMPLE 35 A mixture of 100 g. of 3,5-dimethoxy-n-amylbenzene and 600 g.of pyridine hydrochloride in a 2 liter 3-neck flask equipped withmechanical stirrer is heated with a mantle and allowed to distill untilthe temperature of the vapors reach 210. (Usually 5-10 ml. ofdistillate). A reflux condenser is then added and the solution is heatedunder reflux for 90 minutes. The reaction is allowed to cool to below100 and 1 liter of 2 N hydrochloric acid is added. The cooled solutionis then ex- 20 tracted four times each time with 1 liter of ethylacetate. The extracts were dried (Na SO concentrated under vacuum andthen distilled under high vacuum to give Olivetol, boiling point 165 (1mm Hg.)

EXAMPLE 36 A mixture of 3.6 g. (0.02 mole) of3-methoxy-5-npentyl-2-cyclohexen-l-one and 6.8 g. 60.04 moles of cupricbromide in m1. of benzyl alcohol was reacted by the procedure of Example29 to produce 3- benzyloxy-S-methoxy-n-amylbenzene.

EXAMPLE 37 100 g. of 3-benzyloxy-5-methoxy-n-amylbenzene was reacted inthe manner of Example 35 to produce Olivetol.

We claim:

1. A compound of the formula -benzyl wherein R is an alkyl groupcontaining from 5 to 26 carbon atoms.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION PATENT NO.3,919,322

DATED i November 11, 1975 INVENTOR(S) Arnold Brossi, Antonino Focellaand Sidney' Teitel It is certified that error appears in theabove-identified patent and that said Letters Patent are herebycorrected as shown below:

Column 20, the formula Obenzyl Should be Obenzyl Signed and Scaled thisSeventeenth D3) Of AugTlst 1976 [SEAL] AUG!!! RUTH C. MASON C. MARSHALLDANN Alfflflin fficer Commissioner nj'Parenrs and Trademarks

1. A COMPOUND OF THE FORMULA